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https://www.readbyqxmd.com/read/29458213/selective-targeting-and-degradation-of-doxorubicin-loaded-folate-functionalized-dna-nanocages
#1
Sofia Raniolo, Giulia Vindigni, Alessio Ottaviani, Valeria Unida, Federico Iacovelli, Antonio Manetto, Mariangela Figini, Lorenzo Stella, Alessandro Desideri, Silvia Biocca
Selective targeting is a crucial property of nanocarriers used for drug delivery in cancer therapy. We generated biotinylated octahedral DNA nanocages functionalized with folic acid through bio-orthogonal conjugation chemistry. Molecular modelling indicated that a distance of about 2.5 nm between folic acid and DNA nanocage avoids steric hindrance with the folate receptor. HeLa cells, a folate receptor positive tumour cell line, internalize folate-DNA nanocages with efficiency greater than 40 times compared to cells not expressing the folate receptors...
February 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29458207/co-spray-drying-of-hygroscopic-kanamycin-with-the-hydrophobic-drug-rifampicin-to-improve-the-aerosolization-of-kanamycin-powder-for-treating-respiratory-infections
#2
Mohammad A M Momin, Ian G Tucker, Colin S Doyle, John A Denman, Shubhra Sinha, Shyamal C Das
High dose delivery of drugs to the lung using a dry powder inhaler (DPI) is an emerging approach to combat drug-resistant local infections. To achieve this, highly aerosolizable powders are required. We hypothesized that co-spray-drying kanamycin, a hydrophilic hygroscopic antibiotic, with rifampicin, a hydrophobic antibiotic, would produce inhalable particles with surfaces enriched in rifampicin. Such particles would have higher aerosolization than kanamycin alone, and minimise the mass of powder for inhalation avoiding use of non-active excipients...
February 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29458182/a-direct-gateway-into-the-extracellular-space-unconventional-secretion-of-fgf2-through-self-sustained-plasma-membrane-pores
#3
REVIEW
Julia P Steringer, Walter Nickel
As illustrated by a diverse set of examples in this special issue, multiple mechanisms of protein secretion have been identified in eukaryotes that do not involve the endoplasmic reticulum (ER) and the Golgi apparatus. Here we focus on the type I pathway with Fibroblast Growth Factor 2 (FGF2) being the most prominent example. Unconventional secretion of FGF2 from cells is mediated by direct protein translocation across the plasma membrane. A unique feature of this process is the ability of FGF2 to form its own membrane translocation intermediate through oligomerization and membrane insertion...
February 16, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29458173/deregulation-of-nrf2-are-signaling-pathway-causes-susceptibility-of-dystrophin-deficient-myotubes-to-menadione-induced-oxidative-stress
#4
Su Jin Choi, Hye Sun Kim
Duchenne muscular dystrophy (DMD) is an X chromosome-linked disorder caused by a mutation in the dystrophin gene. Many previous studies reported that the skeletal muscles of DMD patients were more susceptible to oxidative stress than those of healthy people. However, not much has been known about the responsible mechanism of the differential susceptibility. In this study, we established dystrophin knock-down (DysKD) cell lines by transfection of dystrophin shRNA lentiviral particles into C2 cells and found that DysKD myotubes are more vulnerable to menadione-induced oxidative stress than control myotubes...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29458171/toxicology-studies-of-furosine-in-vitro-in-vivo-and-exploration-of-the-related-mechanism
#5
Hui-Ying Li, Lei Xing, Jia-Qi Wang, Nan Zheng
AIM: Furosine is one of the Maillard reaction products (MRPs) and is found in a variety of heat-processed food. Yet its toxicity is still unclear. The present study was designed to assess furosine toxicity in cell models and in CD-1 mice, respectively. METHODS: In vitro, the effects of furosine on the cell viability, cell cycle and apoptosis (Hek293, HepG2, SK-N-SH and Caco2) were detected and evaluated, sensitive cell lines and proper dosage of furosine for further animal experiment were determined, and the mechanisms of toxicity were explored...
February 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29458164/structure-dependent-induction-of-apoptosis-by-hepatotoxic-pyrrolizidine-alkaloids-in-the-human-hepatoma-cell-line-heparg-single-versus-repeated-exposure
#6
Julia Waizenegger, Albert Braeuning, Markus Templin, Alfonso Lampen, Stefanie Hessel-Pras
Pyrrolizidine alkaloids (PA) are secondary plant compounds. PA intoxication in humans causes severe acute and chronic hepatotoxicity. However, the molecular mechanisms of PA hepatotoxicity in humans are not well understood yet. Therefore, we investigated cell death parameters in human HepaRG cells following either single (24 h) or repeated dose treatment (14 d) with structurally different PA of the retronecine (echimidine, senecionine), heliotridine (heliotrine), and otonecine type (senkirkine). After 24 h of exposure only retronecine-type PA were cytotoxic in HepaRG cells and induced apoptosis indicated by a loss of membrane asymmetry, disruption of the mitochondrial membrane potential, and increased pro-caspase and PARP cleavage...
February 16, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29458146/enhanced-anticancer-effects-of-scutellaria-barbata-d-don-in-combination-with-traditional-chinese-medicine-components-on-non-small-cell-lung-cancer-cells
#7
Qian Wang, Narayan Acharya, Zhongwei Liu, Xianmei Zhou, Meghan Cromie, Jia Zhu, Weimin Gao
ETHNOPHARMACOLOGICAL RELEVANCE: Experience-based herbal medicine as a complementary to modern western medicine has triggered an array of studies in quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used to treat different types of cancers, but its molecular mechanism of action is not clearly understood. In this study, we attempted to elucidate the mode of action of a traditional Chinese medicine prescription with a total of 14 components, named Lian-Jia-San-Jie-Fang (LJSJF, in Chinese), where SB works as the "principle" against non-small cell lung cancer (NSCLC) cells...
February 16, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29458131/inhibition-of-hepatitis-b-virus-replication-via-hbv-dna-cleavage-by-cas9-from-staphylococcus-aureus
#8
Yu Liu, Miaoxian Zhao, Mingxing Gong, Ying Xu, Cantao Xie, Haohui Deng, Xueying Li, Hongkai Wu, Zhanhui Wang
Chronic hepatitis B virus (HBV) infection is difficult to cure due to the presence of covalently closed circular DNA (cccDNA). Accumulating evidence indicates that the CRISPR/Cas9 system effectively disrupts HBV genome, including cccDNA, in vitro and in vivo. However, efficient delivery of CRISPR/Cas9 system to the liver or hepatocytes using an adeno-associated virus (AAV) vector remains challenging due to the large size of Cas9 from Streptococcus pyogenes (Sp). The recently identified Cas9 protein from Staphylococcus aureus (Sa) is smaller than SpCas9 and thus is able to be packaged into the AAV vector...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29458070/the-epigenetic-alterations-of-endogenous-retroelements-in-aging
#9
REVIEW
Maurizio Cardelli
Endogenous retroelements, transposons that mobilize through RNA intermediates, include some of the most abundant repetitive sequences of the human genome, such as Alu and LINE-1 sequences, and human endogenous retroviruses. Recent discoveries demonstrate that these mobile genetic elements not only act as intragenomic parasites, but also exert regulatory roles in living cells. The risk of genomic instability represented by endogenous retroelements is normally counteracted by a series of epigenetic control mechanisms which include, among the most important, CpG DNA methylation...
February 16, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29458061/decreased-mcp-1-ccr2-axis-mediated-chemotactic-effect-of-conjunctival-fibroblasts-after-transdifferentiation-into-myofibroblasts
#10
Utako Tsutsumi-Kuroda, Toshihiro Inoue, Akiko Futakuchi, Kohei Shobayashi, Eri Takahashi, Sachi Kojima, Miyuki Inoue-Mochita, Tomokazu Fujimoto, Hidenobu Tanihara
The purpose of this study is to investigate the change in chemotactic effects of human conjunctival fibroblasts (HConFs) after transdifferentiation into myofibroblasts, and to explore related molecular mechanisms. HConFs were treated with 5 ng/mL transforming growth factor (TGF)-β2 for 48 h to induce transdifferentiation into myofibroblasts. The cytokine concentrations in the conditioned media of HConFs were measured by multiplex bead-based immunoassays. The Boyden chamber assay was used to assess the chemotactic effects using the monocyte cell line, THP-1 cells...
February 16, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29458052/regulation-of-proliferation-and-functioning-of-transplanted-cells-by-using-herpes-simplex-virus-thymidine-kinase-gene-in-mice
#11
Mari Tsujimura, Kosuke Kusamori, Chihiro Oda, Airi Miyazaki, Hidemasa Katsumi, Toshiyasu Sakane, Makiya Nishikawa, Akira Yamamoto
Though cell transplantation is becoming an attractive therapeutic method, uncontrolled cell proliferation or overexpression of cellular functions could cause adverse effects. These unfavorable outcomes could be avoided by regulating the proliferation or functioning of transplanted cells. In this study, we used a combination of the herpes simplex virus thymidine kinase (HSVtk) gene, a suicide gene, and ganciclovir (GCV) to control the proliferation and functioning of insulin-secreting cells after transplantation in diabetic mice...
February 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29458020/circrna-circ_0067934-promotes-tumor-growth-and-metastasis-in-hepatocellular-carcinoma-through-regulation-of-mir-1324-fzd5-wnt-%C3%AE-catenin-axis
#12
Qian Zhu, Guiyu Lu, Zihua Luo, Fenfang Gui, Jinghua Wu, Dongwei Zhang, Yong Ni
Recently, increasing evidences demonstrate that circular RNAs (circRNAs) exert very important functions in the progression of human cancers. However, the functions and molecular mechanism of circ_0067934 in hepatocellular carcinoma (HCC) are largely unknown. In the present study, we found that the expression of circ_0067934 was significantly upregulated in HCC tissues and cell lines compared to adjacent normal tissues. Furthermore, we showed that circ_0067934 knockdown remarkably suppressed the proliferation, migration and invasion of Hep3B and HuH7 cells while inducing their apoptosis...
February 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29458018/5-chloro-n4-2-isopropylsulfonyl-phenyl-n2-2-methoxy-4-4-4-methylpiperazin-1-yl-methyl-1h-1-2-3-triazol-1-yl-phenyl-pyrimidine-2-4-diamine-wy-135-a-novel-alk-inhibitor-induces-cell-cycle-arrest-and-apoptosis-through-inhibiting-alk-and-its-downstream-pathways
#13
Mengting Han, Jiwei Shen, Lijing Wang, Yu Wang, Xin Zhai, Yao Li, Meiqiao Liu, Zengqiang Li, Daiying Zuo, Yingliang Wu
Anaplastic lymphoma kinase (ALK)-positive cancers have rising morbidity and mortality in recent years, and novel chemotherapeutic drugs with no drug resistance and high activity for treating ALK-positive cancers are needed urgently. In this study, we investigated the anti-cancer effect of 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-((4-methylpiperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)phenyl)pyrimidine-2,4-diamine (WY-135), a novel ALK inhibitor, on nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) positive cancer cell line Karpas299 and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) positive cancer cell line H2228...
February 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29458013/ago2-rna-immunoprecipitation-reveals-distinct-mirna-targetomes-of-primary-burkitt-lymphoma-tumors-and-normal-b-cells
#14
Agnieszka Dzikiewicz-Krawczyk, Arjan Diepstra, Bea Rutgers, Gertrud Kortman, Debora de Jong, Jasper Koerts, Marian Bulthuis, Tineke van der Sluis, Annika Seitz, Lydia Visser, Klaas Kok, Joost Kluiver, Anke van den Berg
MicroRNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of gene expression. Deregulated miRNA levels have been linked to Burkitt lymphoma (BL) pathogenesis. To date, the number of known pathogenesis-related miRNA-target gene interactions is limited. Here, we determined for the first time the miRNA targetomes of primary BL tumors and normal B cells. AGO2-RNA immunoprecipitation (AGO2-RIP) of two frozen diagnostic BL tissue samples and three CD19+ B-cell samples isolated from routinely removed tonsils revealed distinct miRNA targetomes of BL and normal B cells...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29458011/inflammatory-cytokines-induce-podoplanin-expression-at-the-tumor-invasive-front
#15
Akiko Kunita, Vanessa Baeriswyl, Claudia Meda, Erik Cabuy, Kimiko Takeshita, Enrico Giraudo, Andreas Wicki, Masashi Fukayama, Gerhard Christofori
Tumor invasion is a critical first step in the organismic dissemination of cancer cells and the formation of metastasis in distant organs, the most important prognostic factor and the actual cause of death in most of the cancer patients. We report here that the cell surface protein podoplanin (PDPN), a potent inducer of cancer cell invasion, is conspicuously expressed by the invasive front of squamous cell carcinomas (SCC) of the cervix in patients and in the transgenic HPV/E2 mouse model of cervical cancer...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29458007/a-genomically-characterized-collection-of-high-grade-serous-ovarian-cancer-xenografts-for-preclinical-testing
#16
Paulina Cybulska, Jocelyn M Stewart, Azin Sayad, Carl Virtanen, Patricia A Shaw, Blaise Clarke, Natalie Stickle, Marcus Q Bernardini, Benjamin G Neel
High-grade serous ovarian cancer (HGSC) is the leading cause of morbidity and mortality from gynecologic malignancy. Overall survival remains low, due to the nearly ubiquitous emergence of platinum-resistance and the paucity of effective next-line treatments. Current cell culture-based models show limited similarity to HGSC and are therefore unreliable predictive models for pre-clinical evaluation of investigational drugs. This deficiency could help explain the low overall rate of successful drug development and the decades of largely unchanged approaches to HGSC treatment...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29458000/evidence-for-a-mitochondrial-atp-regulated-potassium-channel-in-human-dermal-fibroblasts
#17
Piotr Bednarczyk, Anna Kicinska, Michal Laskowski, Bogusz Kulawiak, Rafal Kampa, Agnieszka Walewska, Milena Krajewska, Wieslawa Jarmuszkiewicz, Adam Szewczyk
Mitochondrial ATP-regulated potassium channels are present in the inner membrane of the mitochondria of various cells. In the present study, we show for the first time mitochondrial ATP-regulated potassium channels in human dermal fibroblast cells. Using the patch-clamp technique on the inner mitochondrial membrane of fibroblasts, we detected a potassium channel with a mean conductance equal to 100 pS in symmetric 150 mM KCl. The activity of this channel was inhibited by a complex of ATP/Mg2+ and activated by potassium channel openers such as diazoxide or BMS 191095...
February 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29457987/the-rap2c-gtpase-facilitates-b-cell-receptor-induced-reorientation-of-the-microtubule-organizing-center
#18
Jia C Wang, Jeff Y-J Lee, May Dang-Lawson, Caitlin Pritchard, Michael R Gold
When B lymphocytes encounter antigen-bearing surfaces, B-cell receptor (BCR) signaling initiates remodeling of the F-actin network and reorientation of the microtubule-organizing center (MTOC) towards the antigen contact site. We have previously shown that the Rap1 GTPase, an evolutionarily conserved regulator of cell polarity, is essential for these processes and that Rap1-regulated actin remodeling is required for MTOC polarization. The role of Rap2 proteins in establishing cell polarity is not well understood...
February 19, 2018: Small GTPases
https://www.readbyqxmd.com/read/29457979/the-samholides-swinholide-related-metabolites-from-a-marine-cyanobacterium-cf-phormidium-sp
#19
Yiwen Tao, Pinglin Li, Daojing Zhang, Evgenia Glukhov, Lena Gerwick, Chen Zhang, Thomas F Murray, William H Gerwick
Cancer cell cytotoxicity was used to guide the isolation of nine new swinholide-related compounds, named samholides A-I (1-9), from an American Samoan marine cyanobacterium cf. Phormidium sp. Their structures were determined by extensive analysis of 1D and 2D NMR spectroscopic data. The new compounds share an unusual 20-demethyl 44-membered lactone ring comprised of two monomers, and they demonstrate structural diversity arising from geometric isomerization of double bonds, sugar units with unique glyceryl moieties and varied methylation patterns...
February 19, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29457966/combined-treatment-with-valproic-acid-and-5-aza-2-deoxycytidine-synergistically-inhibits-human-clear-cell-renal-cell-carcinoma-growth-and-migration
#20
Wenjin Xi, Xu Chen, Jinbo Sun, Wei Wang, Yi Huo, Guoxu Zheng, Jieheng Wu, Yufang Li, Angang Yang, Tao Wang
BACKGROUND Histone acetylation and DNA methylation are important mammalian epigenetic modifications that participate in the regulation of gene expression. Because dysregulation of histone deacetylase and DNA methyltransferases are hallmarks of malignancy, they have become promising therapeutic targets. In this study, we explored the anti-tumor activity of valproic acid (VPA), a histone deacetylase inhibitor (HDACi) and 5-Aza-2'-deoxycytidine (5-Aza), an inhibitor of DNA methyltransferases, on renal cell carcinoma (RCC) cell lines 786-O and 769-P...
February 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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